S9: cortical dysfunction

Question 1

Define dementia

Answer 1

Umbrella term for loss of memory and other thinking abilities severe enough to interfere with daily life
Result of the progressive destruction of neurones

Question 2

Describe ‘plaques’ in Alzheimer disease

Answer 2

Amyloid precursor protein helps to repair neurones following damage
Alpha and gamma secretase normally chop it up for disposal into soluble parts
However, if beta secretase gets involved, the resulting parts of APP are no longer soluble
Insoluble peptides accumulate outside the cell -> beta amyloid plaques: fill space between neurones & reduce signal transmission

Question 3

What can plaque formation result in?

Answer 3

Can induce an inflammatory response, causing neuronal death
Plaques deposit around blood vessels
-amyloid angiopathy can occur
-weakened blood vessels can bleed

Question 4

Describe ‘tangles’ in Alzheimer disease

Answer 4

Tau proteins play a role in stabilising microtubules with the neuronal cytoskeleton
Beta amyloid plaques induce pathological processes within the neuron -> results in hyperphosphorylation of Tau proteins
Causes a change in shape of Tau proteins, no longer able to support cytoskeleton
Neurone death, also aggregate together into tangles

Question 5

Outline macroscopic changes which occur in Alzheimer disease

Answer 5

General brain atrophy
Narrowing of gyri
Widening of sulci
Ventricular enlargement 
Hippocampus often affected first

Question 6

Describe the role of acetylcholine in Alzheimer’s

Answer 6

ACh concentration and function is decreased in patients

Certain Alzheimer’s medications target this problem – acetylcholinesterase inhibitors

Question 7

Outline the types of Alzheimer disease

Answer 7

Sporadic – causes poorly understood, prevalence increases with age
Familial – early onset dementia, PSEN ½ genes implicated (mutation of gamma secretase), trisomy 21

Question 8

List symptoms of Alzheimer disease

Answer 8

Initially symptoms hard to detect
Short term memory often lost first
Motor and language skills affected 
Long term memory loss
Disorientation 
Immobilisation is linked to cause of death – pneumonia

Question 9

Outline the diagnosis of Alzheimer disease

Answer 9

Are any medications responsible?
Any other disease processes causing symptoms? E.g. hypothyroidism, hypercalcaemia, B12 deficiency, normal pressure hydrocephalus, exclude delirium 
CT scan – show macroscopic changes 
Brain biopsy (postmortem) is only definitive method

Question 10

Describe the treatment for Alzheimer’s

Answer 10

No cure
Acetylcholinesterase inhibitors
Memantine (for advanced cases) – glutamate receptor antagonist

Question 11

Describe Lewy body dementia

Answer 11

Dementia like features early
Parkinsonian features later
Occurs 50-85 years old
More rapid progression

Question 12

What is the pathogenesis of Lewy body dementia?

Answer 12

Caused by misfolding of protein called alpha-synuclein
These misfolded proteins aggregate into Lewy bodies
Main sites of deposition are:
1) Cortex: dementia like symptoms
2) Substantia nigra: parkinsonian features

Question 13

List symptoms and treatment of Lewy body dementia

Answer 13

Cognitive symptoms: distressing hallucinations, depression, REM sleep disorders
Parkinson’s symptoms (later): bradykinesia, resting tremor, stiffness
Treatment: symptom based & levodopa (dopamine analogue)

Question 14

Describe frontotemporal lobe dementia

Answer 14

Aggregated proteins (inclusion bodies) – often younger patients & Tau protein hyperphosphorylation
Affects frontal and temporal lobe
Frontal lobe – behavioural and emotional changes, disinhibition (hostility)
Temporal lobe – language impairment (progressive aphasia)

Question 15

Describe vascular dementia

Answer 15

Heterogenous dementia & can affect multiple sites in brain
Presentation related to area of brain affected
Caused by multiple infarcts and ischaemia -> atherosclerosis, emboli, hypertension & vasculitis
Treatments target risk factors

Question 16

Describe HIV and AIDS dementia

Answer 16

Cause poorly understood
Damage caused by virus itself 
Viral proteins cause injury/inflammation
Result is neuron damage 
AIDS dementia complex can affect behaviour, memory, thinking and movement

Question 17

Describe delirium

Answer 17

An acute, fluctuating syndrome of disturbed consciousness, attention, cognition and perception
Presents suddenly
Categorised as:
1) Hyperactive – agitated/aggressive, delusions
2) Hypoactive – drowsy/withdrawn

Question 18

List the causes of delirium

Answer 18

Drugs
Epilepsy/electrolyte imbalance 
Liver failure/low oxygen
Infection
Retention 
Intracranial 
Uraemia 
Metabolism

Question 19

Describe the treatment for delirium

Answer 19

Minimise/treat precipitating factors
Encourage normal day/night cycle
Allow wandering
For challenging behaviours – distraction techniques
Medications last resort (ie. Haloperidol)

Question 20

List primary causes of headaches

Answer 20

Non-‘life or sight’ threatening, many chronic
Tension-type headache
Migraine
Cluster headache

Question 21

List secondary causes of headaches

Answer 21

Space-occupying lesion
Haemorrhage 
Meningitis 
Giant cell arteritis 
Trigeminal neuralgia 
Medication-overuse

Question 22

List red flags for headaches

Answer 22

Systemic signs and disorders
Neurologic symptoms
Onset new or changed & patient > 50 years old
Onset in thunderclap presentation
Papilloedema, positional provocation & precipitated by exercise

Question 23

Describe tension-type headache

Answer 23

F>M, common, young and young adults
Pathophysiology thought to be due to tension in muscles of head and neck
Generalised – predilection for frontal and occipital regions
Tight/band like, constricting +/- radiating into neck, worse at end of day, recurrent
Triggers: stress, poor posture, lack of sleep
Often responds to simple analgesics

Question 24

Describe migraines

Answer 24

F>M, common, presents early to mid-life
Pathophysiology unclear, possible theories proposed:
1) Neurogenic inflammation of trigeminal sensory neurones innervating large vessels and meninges
2) Alters way pain processed by brain; sensitised to otherwise ignored stimuli

Question 25

Describe the presentation of migraines

Answer 25

Unilateral, temporal or frontal, throbbing, pulsating
Often disabling (need to lie down)
Prolonged headache
Triggers: certain food, menstrual cycle, stress, lack of sleep, strong familial links
Associated symptoms: photophobia, phonophobia, nausea, aura

Question 26

Describe medication over-use headache

Answer 26

F>M, 30-40 year old
Headache present on at least 15 days/month, occurs in patients with pre-existing headache disorder
Using regular analgesics – headache not responding
Variable character, co-exists with depression & sleep disturbance
Discontinue medication (typically resolved completely by 2 months)

Question 27

Describe cluster headaches

Answer 27

M>F
Smoking history major risk factor
Usually begins 30-40 years
Pathophysiology unknown

Question 28

Describe the presentation of a cluster headache

Answer 28

Unilateral, around or behind eye
Severe, intense, often disabling, agitated
Occurs in clusters with periods of remission
Triggers: alcohol, cigarettes, volatile smells, warm temp, lack of sleep
Simple analgesics often ineffective
Ipsilateral autonomic symptoms (red, watery eye, blocked runny nose, ptosis)

Question 29

Describe the presentation of a space-occupying lesion

Answer 29

Gradual, progressive
Worse in mornings
Worsened with posture, cough, Valsalva manoeuvre, straining
Nausea, vomiting, focal neurological or visual symptoms
Clinical exam: focal (unilateral) neurological signs, papilloedema

Question 30

Describe trigeminal neuralgia

Answer 30

F>M
50-60 years
Most caused by compression of CN V due to loop of a blood vessel
5% due to tumours/skull base abnormalities or AV malformations

Question 31

Describe the presentation of trigeminal neuralgia

Answer 31

Unilateral, pain felt in > 1 divisions of CN V
Sharp, stabbing, ‘electric’ shock
Sudden onset
Triggers: light touch to face/scalp, eating, cold wind, combing hair
Simple analgesics not effective, can be difficult to treat

Question 32

Describe temporal arteritis

Answer 32

Vasculitis of large and medium sized arteries of head
F>M, > 50 years
Consider in any >50 year old with abrupt onset of headache & visual disturbance/jaw claudication
Superficial temporal artery commonly involved
Risk of irreversible loss of vision due to involvement of blood vessels supplying CN II